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Agreement between semi-automatic radiographic morphometry and Genant semi-quantitative method in the assessment of vertebral fractures

  • Sanfélix-Genovés J
  • Arana E
  • Sanfélix-Gimeno G
  • Peiró S
  • Graells-Ferrer M
  • Vega-Martínez M
Semi-automatic morphometry is highly reproducible and not time intensive; however, no study has evaluated agreement between semi-automated morphometric methods and the Genant semi-quantitative method performed as a rule by radiologists. Our study shows substantial agreement between both methods; however, semi-automatic morphometry upgrades mild deformities and overestimates the prevalence of fractures. The aim of this study was to evaluate the agreement between radiologists using the Genant semi-quantitative (SQ) method and semi-automated morphometry in the diagnosis of vertebral fractures in post-menopausal women. Cross-sectional study was conducted in 2006-2007 in an age-stratified population-based sample of 824 post-menopausal women over the age of 50. From this population two sets of 95 and 50 X-ray were randomly extracted to test inter-rater agreement and agreement between SQ and semi-automated morphometry, and vertebral fractures were classified according to both methods. The Genant method was used to homogenise the diagnosis of fractures. Agreement was evaluated with weighted kappa. We evaluated each vertebral body independently and also the whole vertebral column (T4-L4) classifying women into the worst grade of fracture. For the qualitative interpretation of the agreement, we used the criteria described by Landis and Koch (Biometrics 33:159-174, 1977). The radiologists' agreement was 98.4% (Kappa, 0.75; 95% CI, 0.42-0.89). Agreement between semi-automated morphometry and SQ reached 97.6% and Kappa was 0.86 (95% CI, 0.66-0.94). In the whole evaluation of the spine semi-automated morphometry overestimates, the prevalence of fractures compared with the radiologists were 15.8% of women with fractures and 7.4% of women with moderate-severe fractures by semi-automated morphometry vs. 8.4% and 3.2% by the SQ method. The negative predictive value for MorphoXpress was 99% while the positive was 40%. Semi-automated morphometry shows high reliability and a substantial agreement with the SQ approach but overestimates the prevalence of fractures. Its role in routine clinical practice is limited because positive results should be reassessed by qualitative or semi-quantitative methods.

Comparability of two different polyacrylamide gel electrophoresis methods for the classification of LDL pattern type.

  • Banuls, C
  • Bellod, L
  • Jover, A
  • Luisa Martinez-Triguero, M
  • Manuel Victor, V
  • Rocha, M
  • Hernandez-Mijares, A
The measurement of small dense low-density lipoprotein (sdLDL) particles is relevant when assessing cardiovascular risk. However, there is as yet no referenced method for the determination of LDL subfractions or a standardized comparison of the methods currently available. Therefore, the aim of this study was to compare the pattern of LDL particles measured by polyacrylamide tube gel electrophoresis (PTGE) and polyacrylamide gradient gel electrophoresis (PGGE) and to correlate the results with triglyceride concentration.

Effect of weight loss on C3 and C4 components of complement in obese patients.

  • Hernandez-Mijares, A
  • Banuls, C
  • Bellod, L
  • Jover, A
  • Sola, E
  • Morillas, C
  • Victor, V
  • Rocha, M
Circulating C3 levels are elevated in obese patients, but how this factor is affected after weight loss through diet is a question that is yet unanswered. Therefore, the aim of this study was to evaluate the effects of weight loss on lipid and hydrocarbonated metabolism parameters and on the levels of C3 and C4 components of complement in obese patients.

Evidence for a relationship between mitochondrial Complex I activity and mitochondrial aldehyde dehydrogenase during nitroglycerin tolerance: Effects of mitochondrial antioxidants

  • Garcia-Bou, R
  • Rocha, M
  • Apostolova, N
  • Herance, R
  • Hernandez-Mijares, A
  • Victor, V
The medical use of nitroglycerin (GTN) is limited by patient tolerance. The present study evaluated the role of mitochondrial Complex I in GIN biotransformation and the therapeutic effect of mitochondrial antioxidants. The development of GIN tolerance (in rat and human vessels) produced a decrease in mitochondrial 02 consumption. Co-incubation with the mitochondria-targeted antioxidant mitoquinone (MQ 10(-6) mol/L) or with glutathione ester (GEE, 10(-4) mol/L) blocked GTN tolerance and the effects of GTN on mitochondrial respiration and aldehyde dehydrogenase 2 (ALDH-2) activity. Biotransformation of GTN depended on the mitochondria being functionally active, particularly mitochondrial Complex I. Tolerance induced mitochondrial ROS production and oxidative stress, though these effects were not detected in HUVEC rho(0) cells or Complex I mutant cells. Experiments performed to evaluate Complex I-dependent respiration demonstrated that its inhibition by GIN was prevented by the antioxidants in control samples. These results point to a key role for mitochondrial Complex I in the adequate functioning of ALDH-2. In addition, we have identified mitochondrial Complex I as one of the targets at which the initial oxidative stress responsible for GIN tolerance takes place. Our data also suggest a role for mitochondrial-antioxidants as therapeutic tools in the control of the tolerance that accompanies chronic nitrate use. (C) 2012 Elsevier B.V. All rights reserved.

In vivo molecular imaging of the GABA/benzodiazepine receptor complex in the aged rat brain

  • Hoekzema, E
  • Rojas, S
  • Herance, R
  • Pareto, D
  • Abad, S
  • Jimenez, X
  • Figueiras, F
  • Popota, F
  • Ruiz, A
  • Flotats, N
  • Fernandez, F
  • Rocha, M
  • Rovira, M
  • Victor, V
  • Gispert, J
The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA A receptor. To visualize BDZ site availability, [C-11]-flumazenil microPET acquisitions were conducted in young and old rats. The data were analyzed and region of interest analyses were applied to validate the voxel-wise approach. We observed decreased [C-11]-flumazenil binding in the aged rat brains in comparison with the young control group. More specifically, clusters of reduced radioligand uptake were detected in the bilateral hippocampus, cerebellum, midbrain, and bilateral frontal and parieto-occipital cortex. Our results support the pertinence of voxel-wise quantification in the analysis of microPET data. Moreover, these findings indicate that the aging process involves declines in neural BDZ recognition site availability, proposed to reflect alterations in GABA A receptor subunit polypeptide expression. (C) 2012 Elsevier Inc. All rights reserved.

Effectiveness of the 2010-2011 seasonal influenza vaccine in preventing confirmed influenza hospitalizations in adults: A case-case comparison, case-control study

  • Puig-Barberà J
  • Díez-Domingo J
  • Arnedo-Pena A
  • Ruiz-García M
  • Pérez-Vilar S
  • Micó-Esparza JL
  • Belenguer-Varea A
  • Carratalá-Munuera C
  • Gil V
  • Schwarz-Chavarri H
Introduction: We estimated influenza vaccine effectiveness (IVE) to prevent laboratory-confirmed influenza-related hospitalizations in patients 18 years old or older during the 2010-2011 influenza season. Methods: We conducted a prospective case-control study in five hospitals, in Valencia, Spain. Study subjects were consecutive emergency hospitalizations for predefined conditions associated with an influenza-like illness episode <8 days before admission. Patients were considered immunized if vaccinated >= 14 days before influenza-like illness onset. Cases were those with a real time reverse transcriptase polymerase chain reaction (RT-PCR) positive for influenza and controls were RT-PCR positive for other respiratory viruses. Adjusted WE was estimated as 100 x (1 - adjusted odds ratio). To account for indication bias we computed adjusted IVE for respiratory syncytial virus related hospitalizations. Results: Of 826 eligible hospitalized patients, 102 (12%) were influenza positive and considered cases, and 116(14%) were positive for other respiratory viruses and considered controls. Adjusted IVE was 54% (95% confidence interval, 11-76%). By subgroup, adjusted WE was 53% (4-77%) for those with high-risk conditions, 59% (16-79%) for those >= 60 years of age, and, 54% (4-79%) for those >= 60 years of age with high-risk conditions. No influenza vaccine effect was observed against respiratory syncytial virus related hospitalization. Conclusion: Influenza vaccination was associated with a significant reduction on the risk of confirmed influenza hospitalization, irrespective of age and high-risk conditions. (C) 2012 Elsevier Ltd. All rights

Antibiotic therapy for pediatric community-acquired pneumonia: do we know when, what and for how long to treat?

  • Esposito S
  • Cohen R
  • Domingo JD
  • Pecurariu OF
  • Greenberg D
  • Heininger U
  • Knuf M
  • Lutsar I
  • Principi N
  • Rodrigues F
  • Sharland M
  • Spoulou V
  • Syrogiannopoulos GA
  • Usonis V
  • Vergison A
  • Schaad UB
Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10-40 cases per 1000 children in the first 5 years of life. Given the clinical, social and economic importance of CAP, there is general agreement that prompt and adequate therapy is essential to reduce the impact of the disease. The aim of this discussion paper is to consider critically the available data concerning the treatment of uncomplicated pediatric CAP and to consider when, how and for how long it should be treated. This review has identified the various reasons that make it difficult to establish a rational approach to the treatment of pediatric CAP, including the definition of CAP, the absence of a pediatric CAP severity score, the difficulty of identifying the etiology, limited pharmacokinetic (PK)/pharmacodynamic (PD) studies, the high resistance of the most frequent respiratory pathogens to the most widely used anti-infectious agents and the lack of information concerning the changes in CAP epidemiology following the introduction of new vaccines against respiratory pathogens. More research is clearly required in various areas, such as the etiology of CAP and the reasons for its complications, the better definition of first- and second-line antibiotic therapies (including the doses and duration of parenteral and oral antibiotic treatment), the role of antiviral treatment and on how to follow-up patients with CAP. Finally, further efforts are needed to increase vaccination coverage against respiratory pathogens and to conduct prospective studies of their impact.


  • García-López R
  • Pérez-Brocal V
  • Diez-Domingo J
  • Moya A
To assess the effect that the rotavirus vaccine RotaTeq may have on the gut microbiota, this study searched for differences in intestinal bacterial composition between vaccinated and unvaccinated children. Bacterial diversity in fecal samples was evaluated by pyrosequencing of the 16S rRNA gene and taxonomic analyses using bioinformatics tools. No evidence of such differences was observed.

13-valent Pneumococcal Conjugate Vaccine Given With Meningococcal C-Tetanus Toxoid Conjugate and Other Routine Pediatric Vaccinations: Immunogenicity and Safety

  • Martinón-Torres F
  • Gimenez-Sanchez F
  • Gurtman A
  • Bernaola E
  • Diez-Domingo J
  • Carmona A
  • Sidhu M
  • Sarkozy DA
  • Gruber WC
  • Emini EA
  • Scott DA
  • 3007 Study Group
Background: As multiple vaccines are administered concomitantly during routine pediatric immunizations, it is important to ascertain the potential interference of any new vaccine on the immune response to the concomitantly administered vaccines. Immune responses to meningococcal serogroup C-tetanus toxoid conjugate vaccine (MnCC-TT) and the diphtheria and tetanus antigens in routine pediatric vaccines (diphtheria, tetanus, acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenza type b [DTaP-HBV-IPV/Hib] and DTaP-IPV+Hib) when given concomitantly with the 13-valent pneumococcal conjugate vaccine (PCV13) were compared with responses when given with PCV7. In addition, the immunogenicity and safety of PCV13 were assessed. Methods: Healthy infants were randomized to receive PCV13 or PCV7 (ages 2, 4, 6 and 15 months), concomitant with MnCC-TT (2, 4 and 15 months), DTaP-HBV-IPV/Hib (2, 4 and 6 months), and DTaP-IPV+Hib (15 months). Results: Immune responses to MnCC-TT and to the diphtheria and tetanus antigens administered with PCV13 were noninferior to the responses observed when the vaccines were administered with PCV7; >= 96.6 (postinfant) and >= 99.4% (posttoddler) subjects achieved prespecified immune response levels to each antigen in each group. After the infant series, >= 93.0% of subjects receiving PCV13 achieved pneumococcal anticapsular immunoglobulin G concentrations >= 0.35 mu g/mL for all serotypes except serotype 3 (86.2%), increasing to 98.1-100% for most serotypes (serotype 3: 93.6%) after the toddler dose. Local and systemic reactions were similar between groups. Conclusions: Immune responses to MnCC-TT, and other childhood vaccines (DTaP-HBV-IPV/Hib, DTaP-IPV+Hib) were noninferior when concomitantly administered with PCV13 compared with PCV7. PCV13 does not interfere with MnCC-TT. PCV13 is highly immunogenic with a favorable safety profile.

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